Actin nucleation-promoting factor WAS

Definition:

Effector protein for Rho-type GTPases that regulates actin filament reorganization via its interaction with the Arp2/3 complex. Important for efficient actin polymerization. Possible regulator of lymphocyte and platelet function. Mediates actin filament reorganization and the formation of actin pedestals upon infection by pathogenic bacteria. In addition to its role in the cytoplasmic cytoskeleton, also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA. Promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs).

References:

[1]. Benjamin R Schrank, et al. Nuclear ARP2/3 drives DNA break clustering for homology-directed repair. Nature. 2018 Jul;559(7712):61-66. [Content Brief]

[2]. Hui-Chun Cheng, et al. Structural mechanism of WASP activation by the enterohaemorrhagic E. coli effector EspF(U). Nature. 2008 Aug 21;454(7207):1009-13. [Content Brief]

[3]. M Symons, et al. Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization. Cell. 1996 Mar 8;84(5):723-34. [Content Brief]

[4]. Matthew D Taylor, et al. Nuclear role of WASp in the pathogenesis of dysregulated TH1 immunity in human Wiskott-Aldrich syndrome. Sci Transl Med. 2010 Jun 23;2(37):37ra44. [Content Brief]

[5]. Giles O C Cory, et al. Phosphorylation of the WASP-VCA domain increases its affinity for the Arp2/3 complex and enhances actin polymerization by WASP. Mol Cell. 2003 May;11(5):1229-39. [Content Brief]

[6]. N Ramesh, et al. WIP, a protein associated with wiskott-aldrich syndrome protein, induces actin polymerization and redistribution in lymphoid cells. Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14671-6. [Content Brief]

[7]. David Chereau, et al. Actin-bound structures of Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 and the implications for filament assembly. Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16644-9. [Content Brief]

[8]. Giles O C Cory, et al. Phosphorylation of tyrosine 291 enhances the ability of WASp to stimulate actin polymerization and filopodium formation. Wiskott-Aldrich Syndrome protein. J Biol Chem. 2002 Nov 22;277(47):45115-21. [Content Brief]

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